Expression and function of Toll-like receptors 2 and 4 in human keratinocytes

Andor Pivarcsi, Laszlo Bodai, Bence Réthi, Anna Kenderessy-Szabó, Andrea Koreck, Márta Széll, Zsuzsanna Beer, Zsuzsanna Bata-Csörgo, Mária Magócsi, Eva Rajnavölgyi, Attila Dobozy, Lajos Kemény

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264 Citations (Scopus)

Abstract

Keratinocytes have the ability to kill pathogenic fungi and bacteria by producing antimicrobial substances. Recent studies suggest that microbial components use signaling molecules of the human Toll-like receptor (TLR) family to transduce signals in various cells. Here we provide evidence that keratinocytes express both TLR2 and TLR4 at the mRNA and protein levels, and show that TLR2 and TLR4 are present in the normal human epidermis in vivo and that their expression is regulated by microbial components. The expression of myelold differentiation protein gene (MyD88), which is involved in the signaling pathway of many TLR, was also demonstrated in keratinocytes. LPS + IFN-γ increased the expression of TLR2 and TLR4 50- and 5-fold respectively. Treatment of keratinocytes with Candida albicans, mannan, Mycobacterium tuberculosis or LPS with IFN-γ resulted in the activation and nuclear translocation of NF-κB. Inhibition of NF-κB blocked the Candida-killing activity of keratinocytes, suggesting that the antimicrobial effect of keratinocytes requires NF-κB activation. LPS + IFN-γ, C. albicans (4 Candida/KC), peptidoglycan (1 μg/ml or M. tuberculosis extract significantly increased IL-8 gene expression after 3 h of treatment (P < 0.05). The increases over the 0-h level were 15-, 8-, 10.8- and 7-fold, respectively. The microbial compound-induced increase in IL-8 gene expression could be inhibited by anti-TLR2 and anti-TLR4 neutralizing antibodies, suggesting that TLRs are involved in the pathogen-induced expression of this pro-inflammatory cytokine. Our findings stress the importance of the role of keratinocytes as a component of innate immunity.

Original languageEnglish
Pages (from-to)721-730
Number of pages10
JournalInternational Immunology
Volume15
Issue number6
DOIs
Publication statusPublished - Jun 1 2003

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Keywords

  • Epidermis
  • Host defense
  • IL-8
  • Innate immunity
  • NF-κB

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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